Back to Search
Start Over
Haploinsufficiency of TNFAIP3 (A20) by germline mutation is involved in autoimmune lymphoproliferative syndrome.
- Source :
- Journal of Allergy & Clinical Immunology; Jun2017, Vol. 139 Issue 6, p1914-1922, 9p
- Publication Year :
- 2017
-
Abstract
- Background Autoimmune diseases in children are rare and can be difficult to diagnose. Autoimmune lymphoproliferative syndrome (ALPS) is a well-characterized pediatric autoimmune disease caused by mutations in genes associated with the FAS-dependent apoptosis pathway. In addition, various genetic alterations are associated with the ALPS-like phenotype. Objective The aim of the present study was to elucidate the genetic cause of the ALPS-like phenotype. Methods Candidate genes associated with the ALPS-like phenotype were screened by using whole-exome sequencing. The functional effect of the identified mutations was examined by analyzing the activity of related signaling pathways. Results A de novo heterozygous frameshift mutation of TNF-α–induced protein 3 (TNFAIP3, A20), a negative regulator of the nuclear factor κB pathway, was identified in one of the patients exhibiting the ALPS-like phenotype. Increased activity of the nuclear factor κB pathway was associated with haploinsufficiency of TNFAIP3 (A20). Conclusion Haploinsufficiency of TNFAIP3 (A20) by a germline heterozygous mutation leads to the ALPS phenotype. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00916749
- Volume :
- 139
- Issue :
- 6
- Database :
- Supplemental Index
- Journal :
- Journal of Allergy & Clinical Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 123255955
- Full Text :
- https://doi.org/10.1016/j.jaci.2016.09.038